title: H63D HFE polymorphisms are associated with increased disease duration and decreased muscle superoxide dismutase-1 expression in amyotrophic lateral sclerosis patients.
abstract: BACKGROUND
  H63D HFE polymorphisms increase the risk of neurodegenerative disorders and, specifically, may increase amyotrophic lateral sclerosis (ALS) risk. Investigating the physiological alterations induced by H63D polymorphisms in ALS patients may elucidate mechanisms by which this genotype alters disease.
  
  
  METHODS
  Clinical measures and muscle biopsies were available from patients previously diagnosed with ALS who underwent HFE genotyping. Clinical outcomes and SOD1 protein expression were analyzed using standard statistical analyses.
  
  
  RESULTS
  ALS patients harboring H63D HFE (n = 16) had 28.1 months longer average disease duration and 39.3% lower muscle SOD1 protein than ALS patients with wild-type HFE (n = 22).
  
  
  CONCLUSIONS
  Combined with previous reports suggesting the H63D polymorphism is associated with ALS, these results support a model wherein the H63D polymorphism is involved in ALS by means of pathways involving SOD1 but may limit cellular damage in individuals who develop disease. The association between HFE genotype and disease duration has important implications for clinical care and treatment trials.
authors.affiliation: George M. Leader Family Laboratory, Department of Neurosurgery, The Pennsylvania State University College of Medicine, 500 University Drive-H110, Hershey, Pennsylvania 17033-0850, USA.
authors.forename: Xiaowei W
authors.initials: XW
authors.lastname: Su
authors.forename: Sang Y
authors.initials: SY
authors.lastname: Lee
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Mitchell
authors.forename: Helen E
authors.initials: HE
authors.lastname: Stephens
authors.forename: Zachary
authors.initials: Z
authors.lastname: Simmons
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D000071020:Hemochromatosis Protein; D006639:Histidine / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology*; D010649:Phenylalanine / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C000606290:SOD1 protein, human; D010649:Phenylalanine; D006639:Histidine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: H63D HFE polymorphism; SOD1; amyotrophic lateral sclerosis; muscle biopsy; neurodegenerative disorders